OVERALL SUMMARY Malaria in the Greater Mekong Subregion (GMS) of Southeast Asia remains an important public health problem. There is immense spatial heterogeneity in malaria distribution, with Myanmar having the highest regional malaria burden. Highly mobile populations crossing porous international borders are a major contributor to parasite introduction and continued transmission. The recent emergence of resistance to the artemisinin (ART) family of drugs as well as to their partner drugs raised global concerns. The vectorial system is highly diverse, and increased outdoor biting and development of insecticide resistance have rendered the two core vector control interventions ? insecticide-treated nets and indoor residue spray less effective. Furthermore, falsified and substandard ART-based combination therapies (ACTs) have become a global crisis. Therefore, the central goal of this program is to improve our understanding of how mobile human populations, parasite drug resistance, and mosquito biology contribute to continuous malaria transmission at international borders so that innovative control strategies can be developed to propel the course of regional malaria elimination. To achieve this overarching objective, we have selected study sites in the international border regions of three GMS countries, Myanmar, China, and Thailand, with drastically different malaria epidemiology to conduct comprehensive research on humans, vectors, and parasites in four interrelated projects. In Project 1, the foundation of the whole program, we will conduct malaria surveillance, monitor human migration and its impact on parasite introduction, and evaluate the effectiveness of the current treatment of the predominant P. vivax malaria. Project 2 will study how environmental changes affect mosquito community structures and malaria transmission, identify whether behavioral changes of major vectors are genetically determined, and determine the extent and mechanisms of insecticide resistance in malaria vectors. In Project 3, we will address the emerging problem of resistance of P. falciparum to both the ART family of drugs and partner drugs through molecular studies of resistance mechanisms and by tracking resistance spread in the GMS. Finally, we want to develop monoclonal antibody-based immunoassays to detect both active ingredients in an ACT, and use our newly developed point-of-care dipstick assays for large-scale assessment of the extent of problem of the falsified and substandard ACTs in the GMS countries using a stratified random sampling approach. This program, built on the scientific achievements of the current ICEMR program and the strong network of international collaborators, aims to dissect the complex interactions between migrant human populations, diverse mosquito vectors, MDR parasites, and falsified and substandard ACTs, which are responsible for continued malaria transmission along international borders. These scientific questions are not only pertinent to the GMS nations, but are also applicable to other malaria regions. Therefore, findings from these studies will bear far-reaching impacts on global malaria elimination.